Endothelial precursor cell-based therapy to target the pathologic angiogenesis and compensate tumor hypoxia

Guillaume Collet, Krzysztof Szade, Witold Nowak, Krzysztof Klimkiewicz, Bouchra El Hafny-Rahbi, Karol Szczepanek, Daisuke Sugiyama, Kazimierz Weglarczyk, Alexandra Foucault-Collet, Alan Guichard, Andrzej Mazan, Mahdi Nadim, Fabienne Fasani, Nathalie Lamerant-Fayel, Catherine Grillon, Stéphane Petoud, Jean Claude Beloeil, Alicja Jozkowicz, Jozef Dulak, Claudine Kieda

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10 Citations (Scopus)

Abstract

Hypoxia-inducing pathologies as cancer develop pathologic and inefficient angiogenesis which rules tumor facilitating microenvironment, a key target for therapy. As such, the putative ability of endothelial precursor cells (EPCs) to specifically home to hypoxic sites of neovascularization prompted to design optimized, site-specific, cell-mediated, drug-/gene-targeting approach. Thus, EPC lines were established from aorta-gonad-mesonephros (AGM) of murine 10.5 dpc and 11.5 dpc embryo when endothelial repertoire is completed. Lines representing early endothelial differentiation steps were selected: MAgEC10.5 and MagEC11.5. Distinct in maturation, they differently express VEGF receptors, VE-cadherin and chemokine/receptors. MAgEC11.5, more differentiated than MAgEC 10.5, displayed faster angiogenesis in vitro, different response to hypoxia and chemokines. Both MAgEC lines cooperated to tube-like formation with mature endothelial cells and invaded tumor spheroids through a vasculogenesis-like process. In vivo, both MAgEC-formed vessels established blood flow. Intravenously injected, both MAgECs invaded Matrigel™-plugs and targeted tumors. Here we show that EPCs (MAgEC11.5) target tumor angiogenesis and allow local overexpression of hypoxia-driven soluble VEGF-receptor2 enabling drastic tumor growth reduction. We propose that such EPCs, able to target tumor angiogenesis, could act as therapeutic gene vehicles to inhibit tumor growth by vessel normalization resulting from tumor hypoxia alleviation.

Original languageEnglish
Pages (from-to)345-357
Number of pages13
JournalCancer Letters
Volume370
Issue number2
DOIs
Publication statusPublished - Jan 28 2016

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Collet, G., Szade, K., Nowak, W., Klimkiewicz, K., El Hafny-Rahbi, B., Szczepanek, K., ... Kieda, C. (2016). Endothelial precursor cell-based therapy to target the pathologic angiogenesis and compensate tumor hypoxia. Cancer Letters, 370(2), 345-357. https://doi.org/10.1016/j.canlet.2015.11.008